Effects and Safety of Non-Pharmacological Therapies of Traditional Chinese Medicine for Coronary Heart Disease: An Overview of Systematic Reviews.
Coronary heart disease (CHD) is currently the leading cause of human death. Non-pharmacological therapy of traditional Chinese medicine (NPTCM) is an important characteristic therapy of traditional Chinese medicine (TCM). Questions concerning the efficacy and safety of NPTCM-related interventions in patients with CHD led us to conduct this overview of systematic reviews (SRs). The Cochrane Library, PubMed, Embase, EBSCO, Epistemonikos, PROSPERO, CNKI, Wanfang Database, and SinoMed were searched without language and publication status restriction from their inception to May 2021, along with grey literature sites and reference lists of included reviews. Systematic reviews comparing NPTCM/a combination of NPTCM and non-TCM interventions with non-TCM interventions/inactive controls for CHD were examined. Two reviewers independently screened titles, abstracts, and full-text articles, and completed data extraction and quality appraisal according to the predefined standards. In total, 1494 titles and abstracts and 66 full-text articles were screened, and a total of 12 SRs (11 with meta-analysis) were finally included. According to PRISMA 2020 checklist, more than 50% of reviews conformed to 80% of 54 items. Consistent evidence of effectiveness or harms across multiple outcomes based on more than one moderate quality review with meta-analysis was found for acupuncture and usual care plus acupuncture/Baduanjin/TCM exercise therapies/TCM emotional therapy. These interventions were mostly evaluated less than 6 months. Acupuncture or acupuncture plus usual care could improve angina symptoms and ECG, and usual care plus Baduanjin/TCM exercise therapies could ameliorate health-related quality of life. Additionally, Baduanjin plus usual care could also improve psychological condition, and it as well as acupuncture could be safe due to no reports on adverse events related to these interventions. TCM emotional therapy plus usual care could benefit patients with CHD and depression.


Administration of the new COMT inhibitor OR-611 increases striatal uptake of fluorodopa.
L-Dopa is metabolized to 3-O-methyldopa (3OMD) by catechol-O-methyltransferase (COMT). This reduces the amount of L-dopa available for entry into brain. We studied the effect of OR-611, a new COMT inhibitor, on plasma and brain 6-[18F]-fluoro-L-dopa (6FD) metabolism in cynomolgus monkeys with positron emission tomography (PET). OR-611 pretreatment substantially reduced plasma 6FD metabolism to 3-O-methylfluorodopa (3OMFD). PET measurements of striatal 6FD concentrations showed an average 2.3-fold increase following OR-611 pretreatment, compared to the same animals in the control state. OR-611 inhibits plasma metabolism of 6FD and increases brain uptake of this L-dopa analog. OR-611 appears to be a promising agent as an adjunct to L-dopa for the treatment of patients with Parkinson's disease.


Mitochondrial DNA mutations may contribute to aging via cell death caused by peptides that induce cytochrome c release.
Mice wherein the wild-type mitochondrial DNA polymerase (pol gamma) is replaced by a proofreading-deficient version are born with mutation frequencies in mitochondrial DNA (mtDNA) much higher than are ever normally seen in old rodents or humans. These mice, however, are phenotypically normal at birth, raising the question regarding how the much lower frequencies observed in normal aging could possibly contribute to the aging process. In contrast, transgenic mice with cardiac-specific expression of a proofreading-deficient poly gamma from birth onwards accumulate mtDNA mutations to levels normally seen in aging. But these mice develop dilated cardiomyopathy suggesting that age-related mtDNA mutations are pathogenic. Using computer simulation, we show that both findings are predicted based on the hypotheses that (1) rare lethal mutations that cause apoptosis underlie the pathogenesis of mutagenesis in mtDNA and (2) most sporadic mtDNA mutations are phenotypically recessive and therefore nonpathogenic. Biochemical evidence is presented that mitochondria with mtDNA mutations generate a peptide that causes the release of cytochrome c, providing a mechanism for the increased apoptosis observed in aging. Simulation also predicts that normal, age-related accumulation of mtDNA mutations causes significant levels of cell death. These findings suggest that mtDNA mutations play an important role in the aging process and that their pathogenic mechanism is linked to apoptosis.


Antiaggregatory activity of 8-epi-prostaglandin F2 alpha and other F-series prostanoids and their binding to thromboxane A2/prostaglandin H2 receptors in human platelets.
8-Epi-prostaglandin F2 alpha (8-epi-PGF 2 alpha) is a nonenzymatic, free radical-catalyzed peroxidation product of arachidonic acid that has potent biological activity, including contraction of vasculature and inhibition of aggregation induced by thromboxane (TX) A2 mimetics. In the present study, we demonstrate that 8-epi-PGF2 alpha could inhibit platelet aggregation induced by the TX mimetics U46619 and I-BOP as well as low-dose collagen but not thrombin or the primary wave of aggregation caused by high-dose ADP. The secondary (TX-dependent) wave of aggregation induced by high-dose ADP, however, was not affected. This suppression was dose dependent where 3.6 and 3.3 microM of 8-epi-PGF2 alpha caused 50% inhibition of platelet aggregation induced by U46619 and I-BOP, respectively, whereas 10 microM caused approximately 72% inhibition of collagen-induced aggregation. In contrast, 8-epi-PGF2 alpha significantly potentiated reversible platelet aggregation in response to low-dose ADP. These results indicate that 8-epi-PGF2 alpha has partial agonist activity. 9 alpha,11 beta-PGF2, a structural isomer of 8-epi-PGF2 alpha, inhibited platelet aggregation induced by collagen, high- and low-dose ADP and thrombin, demonstrating marked differences between structural isomers where 9 alpha,11 beta-PGF2 inhibited platelet aggregation induced by TX-dependent as well as TX-independent stimuli. In addition to platelet aggregation, we performed competition-binding assays on washed human platelets using [125I]BOP to further investigate the interaction of 8-epi-PGF2 alpha and 9 alpha,11 beta-PGF2 with TXA2/PGH2 receptors.(ABSTRACT TRUNCATED AT 250 WORDS)


Molecular basis of cyclic tetra-oligoadenylate processing by small standalone CRISPR-Cas ring nucleases.
Standalone ring nucleases are CRISPR ancillary proteins, which downregulate the immune response of Type III CRISPR-Cas systems by cleaving cyclic oligoadenylates (cA) second messengers. Two genes with this function have been found within the Sulfolobus islandicus (Sis) genome. They code for a long polypeptide composed by a CARF domain fused to an HTH domain and a short polypeptide constituted by a CARF domain with a 40 residue C-terminal insertion. Here, we determine the structure of the apo and substrate bound states of the Sis0455 enzyme, revealing an insertion at the C-terminal region of the CARF domain, which plays a key role closing the catalytic site upon substrate binding. Our analysis reveals the key residues of Sis0455 during cleavage and the coupling of the active site closing with their positioning to proceed with cA4 phosphodiester hydrolysis. A time course comparison of cA4 cleavage between the short, Sis0455, and long ring nucleases, Sis0811, shows the slower cleavage kinetics of the former, suggesting that the combination of these two types of enzymes with the same function in a genome could be an evolutionary strategy to regulate the levels of the second messenger in different infection scenarios.


Race, masks, residency and concern regarding COVID-19 transmission.
To explore sociodemographic predictors for concern regarding COVID-19 transmission and how these factors interact with the identities of others, we conducted a web-based survey where we asked 568 respondents in the United States to indicate their level of COVID-19 concern in response to a series of images with short vignettes of masked and unmasked individuals of different racial/ethnic backgrounds. Using a linear mixed effects model, we found that regardless of the race of the image being presented in the vignette, concern regarding COVID-19 transmission was associated with respondents' older age (b = 0.029, p < 0.001), residing in NYC (b = 0.556, p = 0.009), being heterosexual (b = 1.075, p < 0.001), having higher levels of education, that is, completion of a Bachelor's degree (b = 1.10, p = 0.033) or graduate degree (b = 1.78, p < 0.001), and the person in the vignette being unmasked (b = 0.822, p < 0.001). Asian respondents were more likely than White respondents to be concerned regarding COVID-19. Individuals who self-reported themselves to be at high risk for COVID-19 were more likely to be concerned about COVID-19 over those who considered themselves to be low risk. These findings highlight the importance of acknowledging interactions between race, mask status, and residency in predicting COVID-19 concern.


Kinetic cavity preparation: protection of the cavo-surface enamel.
A significant defect of kinetic cavity preparation systems is damage to cavo-surface sound tooth enamel. The purpose of this study is to establish a protective method for cavo-surface sound tooth enamel during air-powder abrasive system cavity preparation, using protective varnish. A total of 39 extracted human primary teeth were used for this experiment. Protective varnish was applied to the tooth surface in single, double and triple coats. The kinetic instrument was used for cavity preparation. Class V cavities were prepared on the border area of varnish coated and intact tooth surface. After removal of varnish with a supersonic washer, specimens were dried and gold plated with ion-spatter, following which cavity margin enamel was observed through a SEM. Tooth surface enamel where coated with varnish appeared intact and the cavo-surface margin remained at a right angle form. However, tooth surface enamel without varnish coating appeared rough, and the cavo-surface margin exhibited a round shape. It seems likely that kinetic energy was absorbed by the soft varnish coating, thereby protecting the enamel. Protective varnish was found to provide a protective effect for cavo-surface sound enamel, and was also found to promote a sharp edge at the cavo-surface margin, during kinetic cavity preparation.


Isolated left ventricular noncompaction in a case of sotos syndrome: a casual or causal link?
A 16-year-old boy affected by Sotos syndrome was referred to our clinic for cardiac evaluation in order to play noncompetitive sport. Physical examination was negative for major cardiac abnormalities and rest electrocardiogram detected only minor repolarization anomalies. Transthoracic echocardiography showed left ventricular wall thickening and apical trabeculations with deep intertrabecular recesses, fulfilling criteria for isolated left ventricular noncompaction (ILVNC). Some sporadic forms of ILVNC are reported to be caused by a mutation on CSX gene, mapping on chromosome 5q35. To our knowledge, this is the first report of a patient affected simultaneously by Sotos syndrome and ILVNC.


Inhibition of monitoring mechanisms in response to erroneous or veridical feedback. "Virtual lesion" induction by an rTMS study.
External feedback from contextual cues allows humans to behave appropriately in their environments. In the present study, the explicit process of feedback monitoring (an explicit response to veridical vs false feedback) was explored. In addition, the contribution of the prefrontal cortex in this monitoring process was tested by administering an rTMS inhibitory paradigm. Seventeen subjects participated in the study and were required to detect correct vs. incorrect feedback. The experimental task included three main phases: the subject's performance (spatial decisional task); the system's response to the performance (external feedback); and the subject's judgment and response to this external feedback (feedback monitoring). rTMS was performed on the DLPFC. As shown by the behavioural measures (error rate and response times), DLPFC deactivation induced worse performance (higher ER and RT) for both correct and incorrect feedback. Indeed, this prefrontal region seems to contribute to conscious monitoring functions when an explicit response is required. Possible applications to executive function analysis and rehabilitation are suggested.


Impaired posterior frontal sutural fusion in the biglycan/decorin double deficient mice.
Biglycan (Bgn) and decorin (Dcn) are highly expressed in numerous tissues in the craniofacial complex. However, their expression and function in the cranial sutures are unknown. In order to study this, we first examined the expression of biglycan and decorin in the posterior frontal suture (PFS), which predictably fuses between 21 and 45 days post-natal and in the non-fusing sagittal (S) suture from wild-type (Wt) mice. Our data showed that Bgn and Dcn were expressed in both cranial sutures. We then characterized the cranial suture phenotype in Bgn deficient, Dcn deficient, Bgn/Dcn double deficient, and Wt mice. At embryonic day 18.5, alizarin red/alcian blue staining showed that the Bgn/Dcn double deficient mice had hypomineralization of the frontal and parietal craniofacial bones. Histological analysis of adult mice (45-60 days post-natal) showed that the Bgn or Dcn deficient mice had no cranial suture abnormalities and immunohistochemistry staining showed increased production of Dcn in the PFS from Bgn deficient mice. To test possible compensation of Dcn in the Bgn deficient sutures, we examined the Bgn/Dcn double deficient mice and found that they had impaired fusion of the PFS. Semi-quantitative RT-PCR analysis of RNA from 35 day-old mice revealed increased expression of Bmp-4 and Dlx-5 in the PFS compared to their non-fusing S suture in Wt tissues and decreased expression of Dlx-5 in both PF and S sutures in the Bgn/Dcn double deficient mice compared to the Wt mice. Failure of PFS fusion and hypomineralization of the calvaria in the Bgn/Dcn double deficient mice demonstrates that these extracellular matrix proteoglycans could have a role in controlling the formation and growth of the cranial vault.


Unraveling the New Role of Metal-Organic Frameworks in Designing Silicon Hollow Nanocages for High-Energy Lithium-Ion Batteries.
Metal-organic framework (MOF)-derived materials are attracting considerable attention because of the moldability in compositions and structures, enabling greater performances in diverse applications. However, the nanostructural control of multicomponent MOF-based complexes remains challenging due to the complexity of reaction mechanisms. Herein, we present a surface-induced self-nucleation-growth mechanism for the zeolitic imidazolate framework (ZIF) to prepare a new type of ZIF-8@SiO2 polyhedral nanoparticles. We discover that the Zn hydroxide moieties (Zn-OH) within ZIF-8 can trigger the hydrolysis of tetraethyl orthosilicate effectively on the ZIF-8 surface precisely, avoiding the formation of free orthosilicic acid (Si(OH)4) successfully. This is a pioneering work to elucidate the importance of MOF surface properties for preparing multicomponent materials. Then, a novel well-dispersed silicon hollow nanocage (H-Si@C) modified by the carbon was prepared after removal of the ZIF-8 and magnesiothermic reduction. The as-prepared H-Si@C demonstrates an overwhelmingly high lithium storage capability and extraordinary stability in lithium-ion batteries (LIBs), particularly the impressive performances when it was matched with the LiNi0.6Co0.2Mn0.2O2 cathode in a full cell. The MOF surface-induced self-nucleation-growth strategy is useful for preparing more multifunctional materials, while the study of lithium storage performances of the H-Si@C material is practical for LIB applications.


Preparation and reactivation of magnetic biochar by molten salt method: Relevant performance for chlorine-containing pesticides abatement.
Molten salt has been regarded as a versatile and environmental-friendly method for the material preparation and waste destruction. In this work, molten FeCl3 was utilized for the generation of magnetic biochar (MBC) derived from simultaneous activation and magnetization of biomass. The sample characterization indicated that MBC had a rough surface with BET surface area of 404 m2/g and total pore volume of 0.35cm3/g. Highly dispersed Fe3O4 and nitrogen could be deposited on the surface, leading to an excellent magnetization property. The MBC exhibited a great 2,4-Dichlorophenol (2.4-DCP) and atrazine removal performance in solution with the maximum adsorption capacity achieved 298.12 mg/g and 102.17 mg/g. Kinetics results demonstrated that MBC adsorption met the Pseudo-first-order model better. Molten NaOH-Na2CO3 was provided for the re-activation of exhausted MBC. 2,4-DCP was firstly desorbed from the MBC and subsequently destructed by the active species in the melt medium. Chlorine can be captured in the molten alkaline medium from the XRD pattern of residues.The MBC could be easily recovered with a yield of 98.2% and fixed carbon content of 61.0% after the molten salt regeneration process. With no 2,4-DCP detected, 65.5% and 31.69% of initial Cl was found in washing water and residues with the molten NaOH-Na2CO3, respectively. After 4 cycles of regeneration and adsorption, 60.55%-72.22% of initial adsorption capacity can be kept. This preparation and regeneration method can be an effective way to reduce the risk of secondary pollution of chlorinated organic compounds during adsorbent regeneration.Implications: Molten salt (MS) is a salt or multiple salts with a low melting point, and has been applied in many sectors and is regarded as a crucial role in terms of energy, environmental, and resource sustainability. In our paper, magnetic biochar was prepared by one-step activation and magnetization of fir dust using molten FeCl3∙6H2O. Meanwhile, a regeneration method using molten alkaline salt was provided. Magnetic biochar generated in our study performed well in the 2,4-dichlorophenol and atrazine adsorption. After four cycles of regeneration and adsorption, 72.2% of initial 2,4-DCP adsorption capacity can be kept.


Liposome-entrapped diethylstilbestrol effect on prostate gland and plasma testosterone levels in rats.
The effects of liposome-encapsulated diethylstilbestrol (DES) on the size of the ventral prostate gland and total testosterone levels in rats were studied. DES was encapsulated in phosphatidycholine-cholesterol-stearylamine-alpha-tocopherol containing multilamellar liposomes in a molar ratio of 4:5:1:0.01. The liposome suspension or free DES plus blank liposomes were administered sc on days 1, 3, and 5 at a dose of 400, 87, or 12 micrograms/kg. Plasma testosterone values showed a decrease with dose for animals treated with either entrapped DES or free DES. Prostate gland weight per g animal and prostatic protein mg per g animal on day 7 were significantly decreased in the treated animals compared to those in controls dosed with DES plus buffer containing liposomes. In addition, there was a body weight loss for the high dose DES-encapsulated animals and for high and medium dose DES plus blank liposome-treated and blank liposome-treated animals over the treatment period, although only the DES-encapsulated group value was statistically significant (P less than 0.05). Animals at the other doses did not lose weight, but exhibited weight gains which were less than those observed for sham-injected animals. Rats that received 7 micrograms/kg liposome-entrapped DES for 4 weeks had significantly lower prostate gland weights, prostatic protein levels, and testosterone levels than control animals receiving the same regimen of free DES plus blank liposomes. Results from the studies indicate that liposome-entrapped DES was more effective in decreasing the size of the prostate gland and that the desired therapeutic end point (prostate ablation) may be attained with a lower dose of DES, which would decrease the risk of weight loss in the experimental animals.


Imaging of musculoskeletal manifestations in sickle cell disease patients.
Sickle cell disease (SCD) is a hereditary red cell disorder with clinical manifestations secondary to sickling or crescent-shaped distortion of the red blood cells. Major clinical manifestations of SCD include haemolytic anaemia and vaso-occlusive phenomena resulting in ischaemic tissue injury and organ damage. Chronic sequelae of the anaemia and vaso-occlusive processes involving the musculoskeletal system include complications related to extramedullary haematopoiesis, osteonecrosis, myonecrosis and osteomyelitis. Sickle cell bone disease is one of the commonest clinical presentations. Awareness and knowledge of the imaging features related to these complications are essential for early diagnosis and prompt management. In this article, the pathophysiology and key imaging findings related to these complications are reviewed.


Discovery of KIRREL as a biomarker for prognostic stratification of patients with thin melanoma.
There is a great unmet clinical need to identify patients with thin primary cutaneous melanomas (T1, Breslow thickness ≤ 1 mm) who have a high risk for tumour recurrence and death from melanoma. Kin of IRRE-like protein 1 (KIRREL/NEPH1) is expressed in podocytes and involved in glomerular filtration. Screening in the Human Protein Atlas portal revealed a particularly high expression of KIRREL in melanoma, both at the mRNA and protein levels. In this study, we followed up on these findings and examined the prognostic value of KIRREL in a population-based cohort. Immunohistochemical expression of KIRREL was examined in tissue microarrays with a subset of primary tumours and paired lymph node metastases from an original cohort of 268 incident cases of melanoma in the Malmö Diet and Cancer study. KIRREL mRNA expression was examined in 103 melanoma cases in The Cancer Genome Atlas (TCGA). Membranous/cytoplasmic expression of KIRREL was detected in 158/185 (85.4%) primary tumours and 18/19 (94.7%) metastases. High expression of KIRREL was significantly associated with several unfavourable clinicopathological factors. High KIRREL protein expression was an independent factor of reduced recurrence free and melanoma specific survival, particularly in thin melanomas, even outperforming absolute thickness and ulceration (HR = 30.85; 95% CI 1.54-616.36 and HR = 6.32 95% CI 1.19-33.65). High mRNA levels of KIRREL were not significantly associated with survival in TCGA. In conclusion, KIRREL is not only a novel potential diagnostic marker for melanoma, but may also be a useful prognostic biomarker for improved stratification of patients with thin melanoma. These findings may be of high clinical relevance and therefore merit further validation.


An integrative microfluidically supported in vitro model of an endothelial barrier combined with cortical spheroids simulates effects of neuroinflammation in neocortex development.
The development of therapeutic substances to treat diseases of the central nervous system is hampered by the tightness and selectivity of the blood-brain barrier. Moreover, testing of potential drugs is time-consuming and cost-intensive. Here, we established a new microfluidically supported, biochip-based model of the brain endothelial barrier in combination with brain cortical spheroids suitable to detect effects of neuroinflammation upon disruption of the endothelial layer in response to inflammatory signals. Unilateral perfusion of the endothelial cell layer with a cytokine mix comprising tumor necrosis factor, IL-1β, IFNγ, and lipopolysaccharide resulted in a loss of endothelial von Willebrand factor and VE-cadherin expression accompanied with an increased leakage of the endothelial layer and diminished endothelial cell viability. In addition, cytokine treatment caused a loss of neocortex differentiation markers Tbr1, Tbr2, and Pax6 in the cortical spheroids concomitant with reduced cell viability and spheroid integrity. From these observations, we conclude that our endothelial barrier/cortex model is suitable to specifically reflect cytokine-induced effects on barrier integrity and to uncover damage and impairment of cortical tissue development and viability. With all its limitations, the model represents a novel tool to study cross-communication between the brain endothelial barrier and underlying cortical tissue that can be utilized for toxicity and drug screening studies focusing on inflammation and neocortex formation.


Developmental capacities of immature eye-antennal imaginal discs ofDrosophila melanogaster.
The location of the immature eye-antennal discs ofDrosophila melanogaster in embryos and young larvae was established by means of transplantation experiments. The developmental capacities of these immature discs was then investigated by implanting them into larvae which were ready to metamorphose, thus bypassing large portions of embryonic and larval development. Imaginal eye-antennal discs of embryos and first instar larvae are unable to synthesize eye pigments or secrete cuticle. The discs acquire the first detectable competence in the middle of the second instar, 32-36 hours after hatching, when the eye region of the disc becomes competent to synthesize ommochrome pigments and the rest of the disc becomes competent to secrete a thin untanned, transparent cuticle. Competence to synthesize pteridine pigments becomes evident later, 36-42 hours after hatching. The competence to produce specific bristle and hair patterns is acquired still later, 42-56 hours after hatching. Different regions of the eye-antennal disc acquire competence at different times and the acquisition of competence seems to occur in a proximo-distal sequence within both eye and antennal regions of the disc. In the eye region of the disc, the competence to produce proximal structures such as facets appears before the competence to produce ocelli. Similarly, in the antennal region of the disc, the competence to produce the first antennal segment appears before the competence to produce the third antennal segment or arista. Also, the acquisition of competence to produce a specific cuticular pattern occurs four to six hours earlier in the eye region of the disc than in the antennal region. It was also found that the temporal sequence in which differentiation events actually occur during adult development is similar to the temporal sequence in which specific competences are acquired by the growing immature eye-antennal discs.


The Trace Element Zinc in the Composition of Native Chorionic Gonadotropin.
Human chorionic gonadotropin (hCG) is a most important regulator of embryogenesis and spermatogenesis. Equally important for the development of the fetus is the trace element zinc, which is essential for sustainable fetal development. The involvement of hCG and zinc in the first trimester of pregnancy (embryogenesis) led us to question the possibility of their structural cooperation and inclusion in the native molecule chorionic gonadotropin and zinc atoms. At the same time, we found increasing stability of the hormonal structure in the background of hCG interaction with zinc. Thus, the aim of our research was to study the possible zinc presence in the molecule of native hCG. The drug chorionic gonadotropin (1000 IU lyophilisate) was selected as the object of investigation, representing the native hormone that was derived from the urine of pregnant women. For detection of ionized zinc, we used stripping voltammetry and mass spectrometry with inductively coupled plasma at a high resolution (up to 7.10 g/L). The research of nonmineralized samples of chorionic gonadotropin lyophilisate proved its absence in free zinc. Premineralization of the samples made it possible to reveal zinc presence in nine to 17 atoms/molecule of hormone. Detecting bound zinc in the composition of native chorionic gonadotropin confirms its role as an important structural element, capable of producing compound stability and ensuring specific activity during pregnancy. The composition of native chorionic gonadotropin and a major amount of zinc in the bound state, compared to a relatively small amount of free particles, indicates the existence of the sufficiently strong intramolecular bond of hCG and zinc for maintaining active pregnancy. This fact will allow us to design methods for maintaining stable medication during pregnancy on the basis of regulation of trace-element composition in a patient's blood.


Increasing the sensitivity of delta13C and delta15N abundance measurements by a high sensitivity elemental analyzer connected to an isotope ratio mass spectrometer.
A common elemental analyzer system connected to a temperature-controlled gas chromatography (GC) column and coupled to an isotope ratio mass spectrometer was improved to decrease the determination limit for a simultaneous stable isotope ratio measurement of nitrogen and carbon dioxide. The additional use of a special ashtray system to collect the combustion residuals permitted more time-efficient work. These modifications to the elemental analyzer allowed precise measurements to be made down to 1.5 microg nitrogen and 10 microg carbon for stable isotope analysis. Low system background values and an acceptable signal-to-noise ratio have made an additional blank correction for these low sample measurements unnecessary. We provide a precision of this stable isotope analysis for lowest amounts of 1.2-2 microg nitrogen with a standard deviation of +/-0.496 per thousand (n = 27) and for 8.2-15 microg carbon with a standard deviation of +/-0.257 per thousand (n = 31) across different sample runs under stipulated conditions. This application can be established in an automatic mode without cryofocusing procedures.


Trends and Outcomes of Alternative-Access Transcatheter Aortic Valve Replacement.
Alternative access (AA) is still required for a significant proportion of patients undergoing transcatheter aortic valve replacement (TAVR). We sought to compare the clinical outcomes of patients undergoing AA vs transfemoral (TF) access. We retrospectively evaluated the outcomes of patients undergoing AA-TAVR between April 2011 and November 2016, and compared them with those who had TF-TAVR. Chi-square and Mann-Whitney U-tests were used to compare the groups and Kaplan-Meier analysis was performed to estimate long-term survival. TAVR was performed in a total of 600 patients, of which 78 (13%) had AA and 522 (87%) had TF access. Patients undergoing AA were younger, and had higher prevalence of chronic obstructive pulmonary disease, peripheral vascular disease, prior myocardial infarction, and prior sternotomy. Greater than mild paravalvular regurgitation (4.2% vs 0.0%; P=.04) and unplanned vascular surgery (5.4% vs 1.3%; P=.09) were more frequent in the TF group. However, patients who underwent AA had longer hospital stay (median 4 days [interquartile range, 3-7 days] vs 3 days [interquartile range, 3-4 days]; P<.001) and an increased incidence of prolonged ventilation (5.1% vs 1.3%; P=.06), 30-day all-cause (5.1% vs 1.7%; P=.08), and cardiovascular mortality (5.1% vs 1.3%; P=.04). The 6-month (15.7% vs 5.7%; P<.01) and 12-month (16.7% vs 10.2%; P=.07) mortality rates were higher for patients undergoing AA. The usage of AA significantly decreased over time (P=.01), primarily driven by a decrease in transapical (P<.001) and direct aortic access (P=.02). AA-TAVR is associated with an increased incidence of postoperative adverse events, including mortality, when compared with those undergoing TF access.


[Sulbactam and clavulanic acid: studies of enzyme kinetics and synergism with ampicillin and mezlocillin].
Both inhibitors clavulanic acid and sulbactam exhibit high affinity (Ki-values less than 10(-6) mol/l) to the beta-lactamases of gram-negative bacteria with predominant penicillinase activity and lowered affinity to enzymes with cephalosporinase activity (above all clavulanic acid). As compared to sulbactam there was a stronger synergism of clavulanic acid with ampicillin or mezlocillin in those isolates producing either a plasmid-mediated or a chromosomally-mediated penicillinase. In beta-lactamase-overproducing Klebsiella ssp. variants both inhibitors could protect neither ampicillin nor mezlocillin from breakdown-independent of the synergy observed in the corresponding wild-type strains. Moreover, there was a marked synergism between mezlocillin (but not ampicillin) and sulbactam in beta-lactamase-overproducing Enterobacter cloacae variants. There was no strong relation between the amount of enzyme produced and the resulting synergy between inhibitor and antibiotic among clinical isolates. These observations agree with the results obtained for routinely performed susceptibility testing of amoxycillin/clavulanic acid and ampicillin/sulbactam.


Long-range dispersal moved Francisella tularensis into Western Europe from the East.
For many infections transmitting to humans from reservoirs in nature, disease dispersal patterns over space and time are largely unknown. Here, a reversed genomics approach helped us understand disease dispersal and yielded insight into evolution and biological properties of Francisella tularensis, the bacterium causing tularemia. We whole-genome sequenced 67 strains and characterized by single-nucleotide polymorphism assays 138 strains, collected from individuals infected 1947-2012 across Western Europe. We used the data for phylogenetic, population genetic and geographical network analyses. All strains (n=205) belonged to a monophyletic population of recent ancestry not found outside Western Europe. Most strains (n=195) throughout the study area were assigned to a star-like phylogenetic pattern indicating that colonization of Western Europe occurred via clonal expansion. In the East of the study area, strains were more diverse, consistent with a founder population spreading from east to west. The relationship of genetic and geographic distance within the F. tularensis population was complex and indicated multiple long-distance dispersal events. Mutation rate estimates based on year of isolation indicated null rates; in outbreak hotspots only, there was a rate of 0.4 mutations/genome/year. Patterns of nucleotide substitution showed marked AT mutational bias suggestive of genetic drift. These results demonstrate that tularemia has moved from east to west in Europe and that F. tularensis has a biology characterized by long-range geographical dispersal events and mostly slow, but variable, replication rates. The results indicate that mutation-driven evolution, a resting survival phase, genetic drift and long-distance geographical dispersal events have interacted to generate genetic diversity within this species.


BPOZ-2 is a negative regulator of the NLPR3 inflammasome contributing to SARS-CoV-2-induced hyperinflammation.
Inflammation play important roles in the initiation and progression of acute lung injury (ALI), acute respiratory distress syndrome (ARDS), septic shock, clotting dysfunction, or even death associated with SARS-CoV-2 infection. However, the pathogenic mechanisms underlying SARS-CoV-2-induced hyperinflammation are still largely unknown. The animal model of septic shock and ALI was established after LPS intraperitoneal injection or intratracheal instillation. Bone marrow-derived macrophages (BMDMs) from WT and BPOZ-2 KO mouse strains were harvested from the femurs and tibias of mice. Immunohistology staining, ELISA assay, coimmunoprecipitation, and immunoblot analysis were used to detect the histopathological changes of lung tissues and the expression of inflammatory factors and protein interaction. We show a distinct mechanism by which the SARS-CoV-2 N (SARS-2-N) protein targets Bood POZ-containing gene type 2 (BPOZ-2), a scaffold protein for the E3 ubiquitin ligase Cullin 3 that we identified as a negative regulator of inflammatory responses, to promote NLRP3 inflammasome activation. We first demonstrated that BPOZ-2 knockout (BPOZ-2 KO) mice were more susceptible to lipopolysaccharide (LPS)-induced septic shock and ALI and showed increased serum IL-1β levels. In addition, BMDMs isolated from BPOZ-2 KO mice showed increased IL-1β production in response to NLRP3 stimuli. Mechanistically, BPOZ-2 interacted with NLRP3 and mediated its degradation by recruiting Cullin 3. In particular, the expression of BPOZ-2 was significantly reduced in lung tissues from mice infected with SARS-CoV-2 and in cells overexpressing SARS-2-N. Importantly, proinflammatory responses triggered by the SARS-2-N were significantly blocked by BPOZ-2 reintroduction. Thus, we concluded that BPOZ-2 is a negative regulator of the NLPR3 inflammasome that likely contributes to SARS-CoV-2-induced hyperinflammation.


[A PhD completed. General conclusions of doctoral research into regional mouth dryness].
Dry mouth has a complex aetiology which makes proper diagnosis complicated. Until now, dry mouth diagnosis has mainly focused on the overall oral dryness, without taking into account regional differences within the mouth. This research showed, among other things, that there are unique patterns of oral dryness, each with its own cause. For example, patients suffering from Sjogren's syndrome mainly experienced dryness of the posterior of the palate. Patients with dry mouth due to the side effects of medication, in contrast, experienced the front part of the tongue as the driest. These findings suggest that mapping of intraoral dryness may be a useful diagnostic tool to differentiate between possible causes of dry mouth.


Extremely low frequency magnetic field effects on metabolite of Aspergillus niger.
The effect of the extremely low frequency (ELF) magnetic field on citric acid and cellulase production by Aspergillus niger using liquid Charles culture medium was studied during shake flask culture. The cellular suspension was exposed to a magnetic field (t = 4 h, B = 1 mT, and f = 50 Hz). The dependence of yield of citric acid and activity of cellulase on time of exposure and on the value of the magnetic field induction B was measured. Both yield of citric acid and activity of cellulase increased with increasing exposure time and/or induction B, but the quantity of the effect was dependent on the chemical structure of metabolites. The metabolism of citric acid was more sensitive to the magnetic field than that of cellulase. From the measurement of the metabolism dynamics we concluded that the increase in the citric acid and activity of cellulase started immediately after the magnetic field was switched on.


Opposite effect of tumor necrosis factor alpha on granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor-dependent growth of normal and leukemic hemopoietic progenitors.
The effect of recombinant human tumor necrosis factor alpha (TNF-alpha) on normal and chronic myeloid leukemia granulocyte-macrophage progenitors (CFU-GM) growing in semisolid agar cultures in the presence of recombinant granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor was studied. Granulocyte-macrophage colony-stimulating factor-dependent growth of normal and chronic myeloid leukemia bone marrow CFU-GM was greatly enhanced by TNF-alpha at doses of 0.1 to 100 units/ml. Growth enhancement included neutrophil, eosinophil, and monocyte-macrophage colonies and clusters at 7 and 14 days of culture. Since similar results were achieved with highly enriched progenitor cell populations, devoid of accessory cells, an indirect effect on CFU-GM growth through the release by accessory cells of other cytokines upon TNF-alpha stimulation was thus ruled out. By contrast, the same doses of TNF-alpha inhibited the growth of normal CFU-GM in granulocyte colony-stimulating factor-dependent cultures. Taken together, our findings indicate that the final effect of TNF-alpha on normal bone marrow granulocyte-macrophage progenitor growth is dependent on the specific growth factor interacting with it, and that both normal and chronic myeloid leukemia CFU-GM are equally responsive to the combined effects of TNF-alpha and a given colony-stimulating factor.


Specific primers for rapid detection of Microsporum audouinii by PCR in clinical samples.
This report describes application of PCR fingerprinting to identify common species of dermatophytes using the microsatellite primers M13, (GACA)4, and (GTG)5. The initial PCR analysis rendered a specific DNA fragment for Microsporum audouinii, which was cloned and sequenced. Based on the sequencing data of this fragment, forward (MA_1F) and reverse (MA_1R) primers were designed and verified by PCR to establish their reliability in the diagnosis of M. audouinii. These primers produced a singular PCR band of 431 bp specific only to strains and isolates of M. audouinii, based on a global test of 182 strains/isolates belonging to 11 species of dermatophytes. These findings indicate these primers are reliable for diagnostic purposes, and we recommend their use in laboratory analysis.


Therapist and counseling center effects on international students' counseling outcome: A mixed methods study.
We employed a convergent mixed methods design to examine therapist and counseling center effects on international student clients' (ISCs) counseling outcomes. Using the Center for Collegiate Mental Health (CCMH) data set (2015-2017), we conducted a three-level hierarchical linear model with clients (N = 85,110) nested in therapists (N = 1,267), and therapists nested in counseling centers (N = 111), with clients' international status predicting distress (DI) in their last sessions while controlling for initial DI. Compared to domestic students, the average last session DI was significantly higher among ISCs. Random effects were significant, suggesting that some therapists and centers were more effective in their work with ISCs than others. When the proportion of ISCs seen was accounted into the model, we found a cross-level interaction in which the last session DI differences between ISCs and domestic students were significant for centers seeing a small percentage of ISCs but not for centers with large percentages of ISCs in the caseload. Grounded theory analysis of qualitative data from 11 therapists with international backgrounds revealed therapist and center factors that converged with our quantitative findings. Participants reported adhering to general clinical frameworks when working with ISCs given the lack of training on international competence (which may help explain the effectiveness gap), but also noted nuanced culturally-informed components that likely contribute to more effectively working with ISCs. Findings around center effects were complemented by qualitative results emphasizing systemic representation and engagement with diversity, creative outreach efforts, and administrative/leadership support. Implications for practice and research are discussed. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


NiFe-Layered Double Hydroxide Nanosheet Arrays Supported on Carbon Cloth for Highly Sensitive Detection of Nitrite.
Excessive uptake of nitrite has been proven to be detrimental to the ecological system and human health. Hence, there is a rising requirement for constructing effective electrochemical sensors to precisely monitor the level of nitrite. In this work, NiFe-layered double hydroxide nanosheet arrays (NiFe-LDH NSAs) have been successfully fabricated on a carbon cloth (CC) substrate via a facile one-pot hydrothermal route. By integrating the collective merits of macroporous CC and NiFe-LDH NSAs such as superior electrical conductivity, striking synergistic effect between the dual active components, enlarged electrochemically active surface area, unique three-dimensional hierarchical porous network characteristics, and fast charge transport and ion diffusion, the proposed NiFe-LDH NSAs/CC architecture can be served as a self-supporting sensor toward nitrite detection. As a consequence, the resulting NiFe-LDH NSAs/CC electrode demonstrates superior nitrite sensing characteristics, accompanied by broad linear range (5-1000 μM), quick response rate (ca. 3 s), ultralow detection limit (0.02 μM), and high sensitivity (803.6 μA·mM-1·cm-2). Meanwhile, the electrochemical sensor possesses timeless stability, good reproducibility, and strong anti-interference feature. Importantly, the resulting sensor can determine nitrite level in tap and lake water with high recoveries, suggesting its feasibility for practical applications. These findings show that the obtained NiFe-LDH NSAs/CC electrode holds great prospect in highly sensitive and specific detection of nitrite.


Incidence of and risk factors for metachronous gastric cancer after endoscopic resection and successful Helicobacter pylori eradication: results of a large-scale, multicenter cohort study in Japan.
A previous multicenter prospective randomized study from Japan showed that Helicobacter pylori eradication reduced the development of metachronous gastric cancer (MGC) after endoscopic resection for early gastric cancer. MGC risk, however, is not eliminated; yet few studies have evaluated its long-term incidence and risk factors. In this study, we investigated the incidence of and risk factors for MGC in patients who underwent endoscopic resection for early gastric cancer with successful H. pylori eradication. A total of 594 patients who underwent endoscopic resection for early gastric cancer and successful H. pylori eradication at three institutions (National Cancer Center Hospital, University of Tokyo Hospital, and Wakayama Medical University Hospital) were analyzed retrospectively. Annual endoscopic surveillance was performed after initial endoscopic resection. MGC was defined as a gastric cancer newly detected at least 1 year after successful H. pylori eradication. Ninety-four MGCs were detected in 79 patients during the 4.5-year median follow-up period. Kaplan-Meier analysis showed the cumulative incidence of MGC 5 years after successful H. pylori eradication was 15.0 %; the incidence of MGC calculated by use of the person-year method was 29.9 cases per 1000 person-years. Multivariate analysis using the Cox proportional hazards model revealed that male sex, severe gastric mucosal atrophy, and multiple gastric cancers before successful H. pylori eradication were independent risk factors for MGC. Eleven percent of MGCs (10 of 94) were detected more than 5 years after successful H. pylori eradication. Surveillance endoscopy for MGC in patients who have undergone endoscopic resection for early gastric cancer should be performed even after successful H. pylori eradication.


Heterogeneity of myocardial fluoro-18 2-deoxyglucose uptake in patients with apical hypertrophic cardiomyopathy.
We have shown that myocardial glucose metabolism is heterogeneous in patients with hypertrophic cardiomyopathy. It is not known, however, whether glucose metabolism is impaired in patients with apical hypertrophic cardiomyopathy, which is fairly common in Japan. We studied 7 patients with apical hypertrophic cardiomyopathy and 5 normal subjects using fluoro-18 2-deoxyglucose (FDG) and positron emission tomography (PET). We calculated regional FDG fractional uptake and the inter-regional coefficient of variation (CV) of FDG fractional uptake in the interventricular septal, anteroapical, and posterolateral regions. The regional FDG fractional uptake was similar in the 2 groups and among the 3 different segments within each group. However, the inter-regional CV of FDG fractional uptake was increased in the anteroapical wall segment of the patient group compared with the control group and also with the other 2 regions in the patient group. The results did not differ when we studied another 5 patients and 6 normal control subjects with a PET scanner with higher spatial resolution. These data suggest that myocardial glucose metabolism may be impaired in the anteroapical wall segment of patients with apical hypertrophic cardiomyopathy.


Risk Factor of De Novo Urgency and Urge Incontinence After Autologous Fascia Pubovaginal Sling.
Pubovaginal sling is an efficient and safe procedure for stress urinary incontinence without the complications of synthetic sling. Urine retention and de novo urgency are bothersome aftermath of this procedure. We aim to identify potential risk factors for de novo urgency after autologous pubovaginal sling. From 2013 to 2016, 347 patients underwent autologous pubovaginal sling. Age, BMI, pelvic irradiation, use of anticholinergic medication, previous vaginal related surgical histories, "over-tight" technique, and concomitant surgeries were examined for potential risk factors. De novo urgency/urge incontinence was defined as treatment (medication, botulinum toxin injection, sacral neuromodulation) for urge postoperatively and was not noted before surgery. Chi-square and fisher's exact tests were used as statistical analysis. A total of 109 patients underwent autologous rectus fascia pubovaginal sling, after excluding status post urethral diverticulectomy, concomitant diverticulectomy, and concomitant abdominal surgery. Twenty-three (21.1%) patients were treated for de novo urge/urge incontinence, 18 (78.2%) with anticholinergic, 4 (17.3%) with botox injection and 2 (8.69%) with sacral neuromodulation. None but prior pelvic organ prolapse surgery was associated with developing de novo urge/urge incontinence (p=0.026). Patients with prior pelvic organ prolapse surgery were more likely to be at risk of de novo urgency after autologous pubovaginal sling. This study provided more information for preoperative consultation for patients undergoing incontinence surgery.


Ecstatic and gelastic seizures relate to the hypothalamus.
Ecstatic seizures constitute a rare form of epilepsy, and the semiology is diverse. Previously, brain areas including the temporal lobe and the insula have been identified to be involved in clinical expression. The aim of this report is to review changes in ecstatic seizures in a patient before and after operation of a hypothalamic hamartoma, and to scrutinize the relation to gelastic seizures. In this case, the ecstatic seizures disappeared after surgery of the hamartoma but reappeared eleven years later. Clinical information was retrospectively obtained from medical records, interviews, and a questionnaire covering seizure semiology that pertained to ecstatic and gelastic seizures. Our findings imply a possible connection between gelastic and ecstatic seizures, originating from a hypothalamic hamartoma. To our knowledge, this location has not previously been described in ecstatic seizures. Gelastic seizures may in this case were associated with ecstatic seizures. We speclate patients with ecstatic seizures may have an ictal activation of neuronal networks that involves the insula. Our case may add information to the growing knowledge concerning ecstatic seizures.


[Transforming activity of the DNA from human hepatoma cells. The transcription of integrated viral sequences and their cloning].
A monolayer culture of mouse fibroblasts, line NIH/3T3, was transformed by DNA from human hepatoma cell line PLC/PRF/5. The resulting lines of transformed cells differ in their growth characteristics and are capable of producing tumors in nude mice. DNA of these cell lines was found to contain integrated sequences of human DNA and hepatitis B virus DNA. Analysis of transcription showed the amount of virus-specific RNA in the original cell line PLC/PRF/5 to be 20 times as large as in one of the transformed lines. Fragments of DNA of the transformed cells containing virus sequences were cloned, and 400,000 clones were obtained. A clone was identified the insert of which contains a portion of viral genome.


Children with Localized Crohn's Disease Benefit from Early Ileocecal Resection and Perioperative Anti-Tumor Necrosis Factor Therapy.
In pediatric Crohn's disease ileocecal resection is performed reluctantly as postoperative recurrence is frequent. Anti-tumor necrosis factor (TNF) therapy reduces postoperative recurrence rates but increases the risk for infections. We retrospectively reviewed pediatric Crohn's disease patients who underwent ileocecal resection in our center. We compared disease activity and z-scores for height, weight, and body mass index of patients, who continuously received perioperative anti-TNF therapy (TNF + ), with those who did not (TNF-). Of 29 patients (48% females), 13 and 16 were grouped to TNF+ and TNF-, respectively. Patients' characteristics did not differ between groups, except a longer follow-up time in TNF-. We saw significant postoperative improvement but no normalization in z-scores for weight (1.78 vs. 0.77, p < 0.001), body mass index (1.08 vs. 0.22, p < 0.001), and height (0.88 vs. 0.66, p < 0.001). Disease activity improved significantly more in patients receiving anti-TNF therapy (moderate improvement in 83% vs. 31%, p = 0.02). Endoscopic recurrence was more frequent in patients without anti-TNF therapy (80% vs. 20%; p = 0.023), but endoscopic follow-up was incomplete. There was no increase of infections under perioperative anti-TNF therapy (1 patient each; p = 1.000). In patients with localized Crohn's disease an ileocecal resection leads to short-term postoperative improvement of disease activity, body mass index, weight, and growth. For relevant catch-up growth an earlier intervention is necessary. Continuous perioperative anti-TNF therapy had no increased risk of perioperative infections.


MineSDS: A Unified Framework for Small Object Detection and Drivable Area Segmentation for Open-Pit Mining Scenario.
To tackle the challenges posed by dense small objects and fuzzy boundaries on unstructured roads in the mining scenario, we proposed an end-to-end small object detection and drivable area segmentation framework for open-pit mining. We employed a convolutional network backbone as a feature extractor for both two tasks, as multi-task learning yielded promising results in autonomous driving perception. To address small object detection, we introduced a lightweight attention module that allowed our network to focus more on the spatial and channel dimensions of small objects without impeding inference time. We also used a convolutional block attention module in the drivable area segmentation subnetwork, which assigned more weight to road boundaries to improve feature mapping capabilities. Furthermore, to improve our network perception accuracy of both tasks, we used weighted summation when designing the loss function. We validated the effectiveness of our approach by testing it on pre-collected mining data which were called Minescape. Our detection results on the Minescape dataset showed 87.8% mAP index, which was 9.3% higher than state-of-the-art algorithms. Our segmentation results surpassed the comparison algorithm by 1 percent in MIoU index. Our experimental results demonstrated that our approach achieves competitive performance.


Microbial Metabolites of 3-n-butylphthalide as Monoamine Oxidase A Inhibitors.
Novel compounds with antidepressant activity via monoamine oxidase inhibition are being sought. Among these, derivatives of 3-n-butylphthalide, a neuroprotective lactone from Apiaceae plants, may be prominent candidates. This study aimed to obtain the oxidation products of 3-n-butylphthalide and screen them regarding their activity against the monoamine oxidase A (MAO-A) isoform. Such activity of these compounds has not been previously tested. To obtain the metabolites, we used fungi as biocatalysts because of their high oxidative capacity. Overall, 37 strains were used, among which Penicillium and Botrytis spp. were the most efficient, leading to the obtaining of three main products: 3-n-butyl-10-hydroxyphthalide, 3-n-butylphthalide-11-oic acid, and 3-n-butyl-11-hydroxyphthalide, with a total yield of 0.38-0.82 g per g of the substrate, depending on the biocatalyst used. The precursor-3-n-butylphthalide and abovementioned metabolites inhibited the MAO-A enzyme; the most active was the carboxylic acid derivative of the lactone with inhibitory constant (Ki) < 0.001 µmol/L. The in silico prediction of the drug-likeness of the metabolites matches the assumptions of Lipinski, Ghose, Veber, Egan, and Muegge. All the compounds are within the optimal range for the lipophilicity value, which is connected to adequate permeability and solubility.


Innate tissue properties drive improved tendon healing in MRL/MpJ and harness cues that enhance behavior of canonical healing cells.
Development of tendon therapeutics has been hindered by the lack of informative adult mammalian models of regeneration. Murphy Roth's Large (MRL/MpJ) mice exhibit improved healing following acute tendon injuries, but the driver of this regenerative healing response remains unknown. The tissue-specific attributes of this healing response, despite a shared systemic environment within the mouse, support the hypothesis of a tissue-driven mechanism for scarless healing. Our objective was to investigate the potential of MRL/MpJ tendon extracellular matrix (ECM)-derived coatings to regulate scar-mediated healing. We found that deviations in the composition of key structural proteins within MRL/MpJ vs C57Bl/6 tendons occur synergistically to mediate the improvements in structure and mechanics following a 1-mm midsubstance injury. Improvement in mechanical properties of healing MRL/MpJ vs C57Bl/6 tendons that were isolated from systemic contributions via organ culture, highlighted the innate tendon environment as the driver of scarless healing. Finally, we established that decellularized coatings derived from early-deposited MRL/MpJ tendon provisional extracellular matrix (provisional-ECM), can modulate canonical healing B6 tendon cell behavior by inducing morphological changes and increasing proliferation in vitro. This study supports that the unique compositional cues in MRL/MpJ provisional-ECM have the therapeutic capability to motivate canonically healing cells toward improved behavior; enhancing our ability to develop effective therapeutics.


National Study of Excellence and Innovation in Physical Therapist Education: Part 2-A Call to Reform.
This perspective shares recommendations that draw from (1) the National Study of Excellence and Innovation in Physical Therapist Education research findings and a conceptual model of excellence in physical therapist education, (2) the Carnegie Foundation's Preparation for the Professions Program (PPP), and (3) research in the learning sciences. The 30 recommendations are linked to the dimensions described in the conceptual model for excellence in physical therapist education: Culture of Excellence, Praxis of Learning, and Organizational Structures and Resources. This perspective proposes a transformative call for reform framed across 3 core categories: (1) creating a culture of excellence, leadership, and partnership, (2) advancing the learning sciences and understanding and enacting the social contract, and (3) implementing organizational imperatives. Similar to the Carnegie studies, this perspective identifies action items (9) that should be initiated immediately in a strategic and systematic way by the major organizational stakeholders in physical therapist education. These recommendations and action items provide a transformative agenda for physical therapist education, and thus the profession, in meeting the changing needs of society through higher levels of excellence.


Strength and Athletic Adaptations Produced by 4 Programming Models: A Velocity-Based Intervention Using a Real-Context Routine.
To compare the strength and athletic adaptations induced by 4 programming models. Fifty-two men were allocated into 1 of the following models: linear programming (intensity increased while intraset volume decreased), undulating programming (intensity and intraset volume were varied in each session or set of sessions), reverse programming (intensity decreased while intraset volume increased), or constant programming (intensity and intraset volume kept constant throughout the training plan). All groups completed a 10-week resistance-training program made up of the free-weight bench press, squat, deadlift, prone bench pull, and shoulder press exercises. The 4 models used the same frequency (2 sessions per week), number of sets (3 per exercise), interset recoveries (4 min), and average intensity throughout the intervention (77.5%). The velocity-based method was used to accurately adjust the planned intensity for each model. The 4 programming models exhibited significant pre-post changes in most strength variables analyzed. When considering the effect sizes for the 5 exercises trained, we observed that the undulating programming (mean effect size = 0.88-2.92) and constant programming (mean effect size = 0.61-1.65) models induced the highest and lowest strength enhancements, respectively. Moreover, the 4 programming models were found to be effective to improve performance during shorter (jump and sprint tests) and longer (upper- and lower-limb Wingate test) anaerobic tasks, with no significant differences between them. The linear, undulating, reverse, and constant programming models are similarly effective to improve strength and athletic performance when they are implemented in a real-context routine.


High particulate matter burden by cigarillos: A laser spectrometric analysis of second-hand smoke of common brands with and without filter.
Although the global tobacco market of cigarillos is substantial, little is known about their particulate matter (PM) emissions. For exposure risk assessment of cigarillos, the PM fractions PM10, PM2.5, and PM1 of eight cigarillo brands (four with filters) and a reference cigarette were measured. For this purpose, second-hand smoke was generated by an automatic smoke pump in a measuring chamber with a volume of 2.88 m³. The mean particle concentrations of the cigarillos ranged from 2783 μg/m³ to 6686 μg/m³ for PM10, from 2767 μg/m³ to 6585 μg/m³ for PM2.5, and from 2441 to 4680 μg/m³ for PM1. Mean concentrations of the reference cigarette for PM10, PM2.5, and PM1 were 4400 μg/m³, 4335 μg/m³, and 3289 μg/m³, respectively. Filter-tipped cigarillos showed between 5% and 38% lower PM10 and PM2.5 levels, respectively, and between 4% and 30% lower PM1 levels. Our findings show generally high PM emissions for all investigated tobacco products. Therefore, the declaration of PM amounts to government authorities should be mandatory for all tobacco products. Policymakers should ensure that corresponding information will be provided in the future.


The effect of topical anal captopril on resting anal pressure in healthy volunteers: the first human pilot study.
Previous laboratory studies have shown that angiotensin II is produced locally in the rat internal anal sphincter causing potent contraction. The aim of this first human study was to evaluate the safety and manometric effects of topical application of captopril (an ACE inhibitor) on the resting anal pressure in healthy adult volunteers. Ten volunteers, mean age 32.5 years (range, 19-48 years), underwent anorectal manometric evaluation of the mean anal resting pressure (MRAP) and the length of the high-pressure zone (HPZ) before 20 and 60 min after topical application of captopril (0.28 %) cream. Cardiovascular variables (systolic blood pressure, diastolic blood pressure and pulse) were measured before and for up to 1 h after cream application. Side effects were recorded. Adverse events and patient comfort after the cream application were evaluated within a 24-h period by completing a questionnaire. There was no significant change overall in MRAP following captopril administration, although in half the patients, there were reductions in MRAP after treatment. Half the patients had a reduction in the mean resting HPZ length; however, there was no overall difference between pre- and post-treatment values. There was no effect on basic cardiovascular parameters and no correlation between manometric and cardiovascular variables. Topical application of captopril cream may result in a reduction in MRAP in volunteers without anorectal disease. Its use is associated with minimal side effects. It may be a new potential therapeutic option in the treatment of anal fissure. Further studies are required to determine the optimal concentration, dose and frequency of application.


Oxidative amidation and azidation of aldehydes by NHC catalysis.
N-heterocyclic carbene catalyzed oxidative amidations of various aldehydes to the corresponding hexafluoroisopropylesters by using the readily available organic oxidant A are described. The hexafluoroisopropylesters prepared in situ are shown to be highly useful active esters for amide bond formation. In addition, oxidative azidation of aldehydes is presented. These mild organocatalytic processes do not use any transition metal.


Knowledge, aptitudes, and preferences in implant dentistry teaching/training among undergraduate dental students at the University of Barcelona.
Oral implant rehabilitation should be considered a treatment option for any edentulous patient and Implant Dentistry is currently a discipline taught in the undergraduate formation. The level of knowledge acquired and how the students perceive the quality of training in Implant Dentistry could assess to know if it is necessary to improve the syllabus. A questionnaire was developed with 11 questions: Basic knowledge (7); Perception of training received (2); Ways in which students would receive training (2). To be responded anonymously and voluntarily for undergraduates students in the Faculty of Dentistry (University of Barcelona, Spain). One hundred and seven students, 76 third year (Group A) and 31 fourth year (Group B) answered the questionnaire. In Group A, 98.68% of students and in Group B 93.54% believed they were poorly informed; 100% of both groups would prefer to receive more training as part of the degree or as postgraduate training through modular courses imparted by experts (A: 71,05%, B: 70,96%) Training through postgraduate programs or training given by private businesses were the least desirable options (A: 42%, B: 64.51%). Questions about basic knowledge acquired received varying responses, which might indicate a certain level of confusion in this area. The undergraduate syllabus must be revised to include sufficient content and training to allow the student to indicate implant-based treatments based on evidence. Students would prefer training to be included in the undergraduate syllabus.


Disparate diagnostic accuracy of lung function tests as predictors of poor asthma control in children.
Rationale: In practice, asthma control is assessed according to symptom burden and office spirometry. However, spirometry poorly tests peripheral lung function, which may be abnormal in asthma. Impluse oscillometry (IOS) and multiple-breath washout (MBW) are novel methods which measure reactance (X5) and ventilation heterogeneity (VH) in the peripheral lung, but how well these tests reflect asthma control is poorly understood. Objective: To compare the diagnostic accuracy of tests of large airways caliber (FEV1, FEV1/FVC, R20), peripheral zone properties (X5, VH), and airways inflammation (FeNO) as predictors of poor control in asthmatic children (44 poorly controlled/10 controlled). Methods: 54 children enriched in severe asthma completed a symptom-based control scale (ACT/cACT) and lung function tests after overnight bronchodilator withhold. The accuracy of each variable to predict poor control was ranked by area under the receiver operating characteristic (ROC) curve, sensitivity and specificity. Results: Among measures of large airways caliber, the FEV1% had the highest ROC curve area, with low sensitivity but perfect specificity. Among measures of peripheral lung function, X5 and VH in the conducting zone had fair curve areas with higher sensitivity but lower specificity compared to the FEV1%. VH in the acinar zone and FeNO both had poor accuracy. Conclusion: Tests of large airway and peripheral zone lung function performed disparately as predictors of poor control in a sample of children enriched in severe asthma. Further studies in a larger sample with more diverse phenotypic features are necessary to validate this preliminary conclusion.


Timing of colonic necrosis in hemolytic uremic syndrome.
Hemolytic uremic syndrome (HUS) consists of an acute onset of microangiopathic hemolytic anemia, thrombocytopenia, and renal dysfunction. HUS-associated colitis can be seen in up to 100% of patients and is usually associated with severe abdominal pain and distention. Colonic perforation is a complication of HUS that has a reported incidence of 1%-2%, and although there are several case reports in the literature describing perforation of the colon, it is still very difficult to discern the abdominal symptoms associated with HUS colitis from perforation. Four cases of colonic perforation are reported here from a consecutive series of 57 patients, in which a trend in the length of time from the onset of symptoms of HUS to colonic perforation was determined. A review of the literature for cases of HUS-associated colonic perforation was also performed. The time from the onset of HUS symptoms to colonic perforation in our series was similar to that found in the literature review (11 +/- 5 vs 14 +/- 8 days). Awareness that this complication has a tendency to occur towards the end of the 2nd week during the course of HUS is essential to avoid an unnecessary and untimely surgical intervention.


Nanotechnology: a new look.
A recently published report has reassessed the meanings of nanoscience and nanotechnology and considered the opportunities and hazards that arise within this area. Some of the factors relevant to medical nanotechnology are considered here.


Systematic discovery of mutation-specific synthetic lethals by mining pan-cancer human primary tumor data.
Two genes are synthetically lethal (SL) when defects in both are lethal to a cell but a single defect is non-lethal. SL partners of cancer mutations are of great interest as pharmacological targets; however, identifying them by cell line-based methods is challenging. Here we develop MiSL (Mining Synthetic Lethals), an algorithm that mines pan-cancer human primary tumour data to identify mutation-specific SL partners for specific cancers. We apply MiSL to 12 different cancers and predict 145,891 SL partners for 3,120 mutations, including known mutation-specific SL partners. Comparisons with functional screens show that MiSL predictions are enriched for SLs in multiple cancers. We extensively validate a SL interaction identified by MiSL between the IDH1 mutation and ACACA in leukaemia using gene targeting and patient-derived xenografts. Furthermore, we apply MiSL to pinpoint genetic biomarkers for drug sensitivity. These results demonstrate that MiSL can accelerate precision oncology by identifying mutation-specific targets and biomarkers.


Evaluating the Association of Face Covering Mandates on COVID-19 Severity by State.
During the COVID-19 pandemic in the United States, mitigation measures were implemented on a state-by-state basis. Governors were responsible for establishing interventions appropriate for their states and the timing of implementation. This paper evaluated the association between the presence and timing of a mask mandate and the severity of the COVID-19 epidemic by state. The states were divided into 3 categories based on when the governors of each state implemented a mask mandate: Early (mask mandate implemented between March 2020 and June 2020), Late (July 2020-December 2020), and Never (no mask mandate implemented). The rates of hospitalizations and mortality (per 100 000) were assessed at the different time points during the pandemic across these categories from March to December 2020. The mortality rates across all 3 groups were observed to be highest in the beginning and toward the end of the pandemic in 2020 with the peak observed in the Early group between April and May 2020. Also, the rates of hospitalization increased steadily across all groups. The Early mask group was comprised of 86.7% and 13.3% states with Democratic and Republican governors respectively, and no states in the Never category had Democratic governors. These results support the benefit of implementing a mask mandate to minimize the impact of the COVID-19 pandemic and the role of political affiliation of governors on that impact.


3-(3-Chloro-phen-yl)-1-methyl-3,3a,4,9b-tetra-hydro-1H-chromeno[4,3-c]isoxazole-3a-carbonitrile.
In the title compound, C(18)H(15)ClN(2)O(2), the five-membered isoxazole ring adopts an envelope conformation [the deviation of the N atom is 0.3154 (15) Å] and the six-membered pyran ring adopts a half-chair conformation. The mean plane through all atoms of the isoxazole ring forms dihedral angles of 47.98 (8)° with the mean plane of the chromene ring system and 75.10 (9)° with the chloro-benzene ring.


Effects of willow and Sedum alfredii Hance planting patterns on phytoremediation efficiency under AC electric field.
Heavy metal contamination to soil is tricky due to its difficult removal, long retention time, and biomagnified toxicity. The green and low-cost phytoremediation with electric field treatment and planting pattern selection is an emerging and more effective approach to remove heavy metals from soils. In this study, alternating current (AC) electric field-assisted phytoremediation was examined with different planting patterns, i.e., monoculture willow (Salix sp.), monoculture Sedum alfredii Hance, and interplanting of willow and S. alfredii. AC electric field greatly increased phytoremediation efficiency to soil cadmium (Cd) regardless of planting patterns, either single plant species of willow or S. alfredii. The Cd removal capacity of willow and S. alfredii raises apparently under 0.5 V cm-1 AC electric field. Under different planting patterns of AC electric field treatment, Cd accumulation in the whole plant by interplanting was 5.63 times higher than monoculture willow, but only 0.75 times as high as monoculture S. alfredii. The results showed that AC electric field-assisted interplanting of willow and S. alfredii is a promising remediation technique for efficiently clean-up Cd-contaminated soil.


Amyloid-forming proteins alter the local mechanical properties of lipid membranes.
A diverse number of diseases, including Alzheimer's disease, Huntington's disease, and type 2 diabetes, are characterized by the formation of fibrillar protein aggregates termed amyloids. The precise mechanism by which aggregates are toxic remains unclear; however, these proteins have been shown to interact strongly with lipid membranes. We investigated morphological and mechanical changes in model lipid bilayers exposed to amyloid-forming proteins by reconstructing the tapping forces associated with atomic force microscopy (AFM) imaging in solution. Tip/sample tapping forces contain information regarding mechanical properties of surfaces. Interpretation of the mechanical changes in the bilayers was aided by numerical simulations of the entire AFM experiment. Amyloid-forming proteins disrupted distinct regions of the bilayer morphology, and these regions were associated with decreased Young's modulus and adhesive properties. These changes in bilayer mechanical properties upon exposure to amyloid-forming proteins may represent a common mechanism leading to membrane dysfunction in amyloid diseases.


Serum paraoxonase 1 activity in patients with iron deficiency anemia.
In this study we aimed to detect paraoxonase 1 (PON-1) activity in iron deficiency anemia (IDA) and to compare it with healthy controls by observing the change after iron therapy. In this study, 50 adult patients with IDA and 40 healthy subjects were enrolled. All patients were analyzed at the beginning and after treatment according to laboratory assessments. Mean paraoxonase and arylesterase activities in the iron deficiency anemia group were significantly lower than mean activities of the control group (102.4 ±19.2 U/l and 163.3 ±13.68 U/l, respectively and 157.3 ±26.4 U/l and 256.1 ±24.6 U/l, respectively; p = 0.0001 for both). Paraoxonase and arylesterase activities significantly increased after treatment for IDA (143.2 ±13.9 and 197.6 ±27.9 U/l, respectively, p = 0.0001). Mean activities after treatment with iron were significantly lower than mean activities in the control group (p = 0.002; p = 0.0001 respectively). Paraoxonase and arylesterase activities in patients with IDA significantly increased after treatment with iron therapy. In adults IDA may also be one of the factors associated with increased risk of atherosclerosis.


Values clarification and ethical decision making.
Ethical decision making at the bedside has become an integral part of nursing care delivery. Health care providers have long been practicing clinical ethics as evidenced by their codes of practice. Still, bedside ethical decision making has really just become more formalized in the 1980s through the establishment of hospital ethics committees. The decisions of the 1980s and 1990s have become more difficult as well mostly because of advanced medical technology, the increased number of people now involved in the decision-making process, and most importantly, the recognition of patient autonomy in the decision-making process.


[Multifocal atrial tachycardia in infancy].
Four infants with multifocal atrial tachycardia are presented. They all displayed the typical ECG-findings of this particular form of supraventricular tachycardia: at least 3 different P-waves; varying atrial rate over 100 beats per minute; an isoelectric baseline between P-waves and a permanent variation of PP-, PR- and RR-intervals. One baby had a truncus arteriosus communis, the other 3 were healthy except for their rhythm disorder. In 2 of our patients, the multifocal atrial tachycardia was already present at birth, in the other 2 infants it became apparent at age 2 and 4 months respectively. Two children were asymptomatic, the other 2 had a slightly enlarged heart and some evidence of pulmonary venous congestion on chest roentgenogram. All 4 patients received digoxin. The tachycardia disappeared in 2 cases under but without definite causal relation to that treatment. In the 2 other cases the tachycardia persists in spite of treatment. Multifocal atrial tachycardia is a rare form of rhythm disturbance in infancy; it is difficult to treat but frequently resolves spontaneously within the first year of life.


Theoretical studies of potential energy surface and rotational spectra of Xe-H(2)O van der Waals complex.
In this work we report an ab initio intermolecular potential energy surface and theoretical spectroscopic studies for Xe-H(2)O complex. The ab initio energies are calculated with CCSD(T) method and large basis sets (aug-cc-pVQZ for H and O and aug-cc-pVQZ-PP for Xe) augmented by a {3s3p2d2f1g} set of bond functions. This potential energy surface has a global minimum corresponding to a planar and nearly linear hydrogen bonded configuration with a well depth of 192.5 cm(-1) at intermolecular distance of 4.0 A, which is consistent with the previous determined potential by Wen and Jager [J. Phys. Chem. A 110, 7560 (2006)]. The bound state calculations have been performed for the complex by approximating the water molecule as a rigid rotor. The theoretical rotational transition frequencies, isotopic shifts, nuclear quadrupole coupling constants, and structure parameters are in good agreement with the experimental observed values. The wavefunctions are analyzed to understand the dynamics of the ground and the first excited states.


A protocol for evaluation of Rett Syndrome symptom improvement by metabolic modulators in Mecp2-mutant mice.
Mouse models recapitulate many symptoms of Rett Syndrome, an X-linked disorder caused by mutations in methyl-CpG-binding protein 2 (MECP2). The study of Mecp2-null male mice has provided insight into pathogenesis of the disorder; most recently, dysregulation of cholesterol and lipid metabolism. Perisymptomatic treatment with statin drugs successfully mitigates the effects of this metabolic syndrome, increases longevity and improves motor function. Described here is a metabolic drug screening protocol and timeline for symptom evaluation in Mecp2-mutant mice. Specifically, mice are treated twice weekly with a compound of interest alongside subjective health assessments, bi-weekly body composition measurements and blood chemistries. Throughout treatment, behavioral phenotyping tests are carried out at specific time points. This protocol is highly adaptable to other neurological diseases; however, the time for completion depends on the specific mutant model under study. The protocol highlights the use of several different CPMo protocols to carry out testing in a preclinical model.


Usefulness of flexible colonoscopic microwave coagulation therapy for a colorectal anastomotic stricture.
Several methods of treatment for benign anastomotic strictures after anterior resection have been described. We describe a simple, safe, effective, and inexpensive method for treating benign colorectal anastomotic stricture by means of microwave coagulation under flexible colonoscopic visualization. Eighteen patients with rectal or rectosigmoidal cancer underwent low anterior resection or anterior resection without colonic pouch and colorectal anastomosis by a double-stapling technique with PCEEA. Two of 18 patients (11.1 percent) developed an anastomotic stenosis. A microwave electrode was passed through the biopsy channel of the flexible colonoscope. Under flexible colonoscopic visualization, microwave irradiation was performed at four points (3, 6, 9, and 12 o'clock) in the stricture site because of granulation scar to obtain an adequately coagulated area. No bougies were performed thereafter. The anastomotic strictures could be dilated adequately, the patients could defecate satisfactorily, and their abdominal distentions and bowel symptoms were resolved. No complications occurred. No occurrence of restricture has been observed. Flexible endoscopic, microwave coagulation therapy is a useful, simple, effective, and safe method for the treatment of benign colorectal anastomotic strictures.


Colony-structure variation and interspecific competitive ability in the invasive Argentine ant.
The success of some invasive species may depend on phenotypic changes that occur following introduction. In Argentine ants (Linepithema humile) introduced populations typically lack intraspecific aggression, but native populations display such behavior commonly. We employ three approaches to examine how this behavioral shift might influence interspecific competitive ability. In a laboratory experiment, we reared colonies of Forelius mccooki with pairs of Argentine ant colonies that either did or did not exhibit intraspecific aggression. F. mccooki reared with intraspecifically non-aggressive pairs of Argentine ants produced fewer eggs, foraged less actively, and supported fewer living workers than those reared with intraspecifically aggressive pairs. At natural contact zones between competing colonies of L. humile and F. mccooki, the introduction of experimental Argentine ant colonies that fought with conspecific field colonies caused L. humile to abandon baits in the presence of F. mccooki, whereas the introduction of colonies that did not fight with field colonies of Argentine ants resulted in L. humile retaining possession of baits. Additional evidence for the potential importance of colony- structure variation comes from the Argentine ant's native range. At a site along the Rio de la Plata in Argentina, we found an inverse relationship between ant richness and density of L. humile (apparently a function of local differences in colony structure) in two different years of sampling.


History and epidemiology of antibiotic susceptibilities of Neisseria gonorrhoeae.
Neisseria gonorrhoeae is a common causative microorganism of male urethritis. The most important problem with this infectious disease is antibiotic resistance. For instance, in the 1980's-1990's, most studies showed almost 100% susceptibility of N. gonorrhoeae to the representative cephalosporins, cefixime and cefpodoxime. By the late 1990s, the reported susceptibility decreased to 93.3-100% and further decreased to 82.9-100% in the early 2000's. However, reported susceptibility was revived to 95.8-100% in the late 2000's to 2010's. The susceptibility of N. gonorrhoeae to penicillins varied in different countries and regions. A 2002 Japanese study showed a resistance ratio of about 30% and while Laos, China and Korea showed 80-100% resistance. Fluoroquinolones have shown a dramatic change in their effect on N. gonorrhoeae. In the early 1990's, 0.3-1.3% of N. gonorrhoeae showed low susceptibility or resistance to ciprofloxacin in the US but this figure jumped to 9.5% by 1999. In Asia, N. gonorrhoeae ciprofloxacin resistance or lower susceptibility was about 80-90% in the early 2000's and this trend continues to the present day. Azithromycin is currently the possible last weapon for N. gonorrhoeae treatment per oral administration. The susceptibility of N. gonorrhoeae to azithromycin was 100% in Indonesia in 2004 and the latest study from Germany showed 6% resistance in strains from 2010-2011. This review summarizes the history and epidemiology of N. gonorrhoeae antibiotic susceptibilities, for which the most frequently used antibiotics vary between countries or regions.


Evaluation of a carbonic anhydrase mimic for industrial carbon capture.
Zinc(II) cyclen, a small molecule mimic of the enzyme carbonic anhydrase, was evaluated under rigorous conditions resembling those in an industrial carbon capture process: high pH (>12), nearly saturated salt concentrations (45% K2CO3) and elevated temperatures (100-130 °C). We found that the catalytic activity of zinc cyclen increased with increasing temperature and pH and was retained after exposure to a 45% w/w K2CO3 solution at 130 °C for 6 days. However, high bicarbonate concentrations markedly reduced the activity of the catalyst. Our results establish a benchmark level of stability and provide qualitative insights for the design of improved small-molecule carbon capture catalysts.


Feminist Semiotics of "Safe": Intimate Violence in the Time of Pandemic.
This article explores the discursive politics of intimate partner violence during the first COVID-19 lockdown in Israel. It asks how, despite greater awareness and recognition, intimate violence disappeared from the mindset of those managing the pandemic, even as it soars. The analysis traces the conditions that enable the dialectic of presence-disappearance, by reading the ideological prescriptions in policy papers, parliamentary debates, court appeals, and media debates. I argue that disregard of intimate violence is made possible by the idealization of home and family as spaces of security and protection, coupled with the mobilization of militaristic measures and discourses.


The Effects of Empiric Antireflux Treatment on Laryngopharyngeal and Gastroesophageal Reflux Disease.
This study aims to investigate the effects of empiric lansoprazol therapy on laryngopharyngeal (LPR) and gastroesophageal (GOR) reflux symptoms and laryngological findings. Sixty-seven patients with suspected LPR related symptoms were prospectively analyzed in this study. Following eleven symptoms were asked to patients using LPR symptom questionnaire; sore throat, throat burning, throat clearing, globus sensation, cough, halitosis, dysphonia, dysphagia, postnasal dripping, vocal fatigue and sputum. GOR symptoms were evaluated with the Frequency Scale for the Symptoms of Gastroesophageal Reflux Disease (FSSG) questionnaire consist of twelve symptoms. Posterior larynx, arytenoids and interarytenoid area were evaluated with a 70° endoscope. Erythema, edema and nodularity were graded separately using 4 point severity scale to examine laryngeal signs. All patients were treated using 30 mg lansoprazole once daily for four weeks. After the end of medication, symptoms and laryngoscopic signs were evaluated again with the same method. The pretreatment and posttreatment values were compared with statistical analyses. There was a statistically significant decrease in LPR symptom scores and total scores of FSSG. The severity of nodularity in the posterior larynx, arytenoids and interarytenoid area was improved after treatment. There was no statistically significant difference in erythema on each area larynx. Edema in the posterior larynx and interarytenoid area was improved but there was no change on the edema of arytenoids. A short period of empiric antireflux treatment has a significant improving effect on all LPR symptoms and most of GOR symptoms. However, it was insufficient on laryngeal signs. Further research is needed to investigate longer times of treatment for the complete resolution of symptoms and signs.


Up-regulated expression of decay-accelerating factor (CD55) confers increased complement resistance to sprouting neural cells.
We studied gene expression in relation to induced neural differentiation in a human neural crest-derived cell line, Paju. Messenger RNA isolated before and after treatment with phorbol 12-myristate 13-acetate was analyzed by differential display reverse transcription PCR. A strongly up-regulated expression of decay-accelerating factor (DAF, CD55) was found to parallel the induced neural sprouting while the expression of two other complement regulatory proteins (CD59/protectin, CD46/membrane cofactor protein) remained unaltered during neural differentiation. The increased membrane expression of DAF, which was also seen on neural processes and growth cones, conferred elevated resistance to complement-mediated lysis. Our findings suggest that in sprouting neurons DAF expression is up-regulated to provide additional complement resistance to pathfinding axons/dendrites invading new environment. It is also suggested that membrane expression of DAF may constitute a marker of growing and regenerating neurons.


Development of gene therapies-lessons from nusinersen.
The nusinersen development and approval process provide important lessons regarding the pathway to marketing approval for gene therapies. These lessons emphasize rigorous clinical trial design, flexibility in trial design and analysis, a collaborative effort with regular communications between the drug developer and the Food and Drug Administration (FDA), and use of FDA's expedited programs. These lessons are critical to the development of gene therapies for the treatment of serious or life-threatening rare diseases.


Age affects spontaneous activity and depolarizing afterpotentials in isolated gonadotropin-releasing hormone neurons.
Neuronal activity underlying the pulsatile secretion of GnRH remains poorly understood, as does the endogenous generation of such activity. It is clear that changes at the level of the hypothalamus are taking place during reproductive aging, yet virtually nothing is known about GnRH neuronal physiology in aging and postreproductive animals. In these studies, we performed cell-attached and whole-cell recordings in GnRH-enhanced green fluorescent protein neurons dissociated from young (3 months), middle-aged (10 months), and old (15-18 months) female mice. All mice were ovariectomized; half were estradiol replaced. Neurons from all ages fired spontaneously, most in a short-burst pattern that is characteristic of GnRH neuronal firing. Membrane characteristics were not affected by age. However, firing frequency was significantly reduced in neurons from old animals, as was spike patterning. The amplitude of the depolarizing afterpotential, evoked by a 200-msec current pulse, was significantly smaller in aged animals. In addition, inward whole-cell currents were reduced in estradiol-treated animals, although they were not significantly affected by age. Because depolarizing afterpotentials have been shown to contribute to prolonged discharges of activity after a very brief excitatory input, a decreased depolarizing afterpotential could lead to attenuated pulses in older animals. In addition, decreases in frequency and pattern generation could lead to improper information coding. Therefore, changes in the GnRH neuron during aging could lead to dysregulated activity, potentially resulting in the attenuated LH pulses observed in the transition to reproductive senescence.


"Affective contingencies in the affiliative domain: Physiological assessment, associations with the affiliation motive, and prediction of behavior": Correction to Dufner et al. (2015).
Reports an error in "Affective contingencies in the affiliative domain: Physiological assessment, associations with the affiliation motive, and prediction of behavior" by Michael Dufner, Ruben C. Arslan, Birk Hagemeyer, Felix D. Schönbrodt and Jaap J. A. Denissen (Journal of Personality and Social Psychology, 2015[Oct], Vol 109[4], 662-676). In this article an erroneous statement was made regarding the high cutoff filter for the EMG raw signal. The high cutoff filter reported in Appendix B in the Technical Details of the EMG Recording Procedure section should be 300 Hz. (The following abstract of the original article appeared in record 2015-37761-001.) According to classical motive disposition theory, individuals differ in their propensity to derive pleasure from affiliative experiences. This propensity is considered a core process underlying the affiliation motive and a pervasive cause of motivated behavior. In this study, we tested these assumptions. We presented participants with positive affiliative stimuli and used electromyography to record changes in facial muscular activity that are indicative of subtle smiling. We were thus able to physiologically measure positive affect following affiliative cues. Individual differences in these affective contingencies were internally consistent and temporally stable. They converged with affiliation motive self- and informant reports and picture story exercise scores, indicating that they are partly accessible to the self, observable to outsiders, and overlap with implicit systems. Finally, they predicted affiliative behavior in terms of situation selection and modification across a wide variety of contexts (i.e., in daily life, the laboratory, and an online social network). These findings corroborate the long-held assumption that affective contingencies represent a motivational core aspect of affiliation. (PsycINFO Database Record


Self-Reported Ability to Walk, Run, and Lift Objects among Older Canadians.
Aims. The purpose of the study was to develop new self-report instruments to measure the ability to walk, run, and lift objects and describe the distribution of these abilities among older Canadians. Methods. Questions were developed following a focus group. We carried out an online survey among members of the Canadian Association of Retired Persons. The distribution of each ability was described and presented graphically according to age, sex, and number of health conditions. We calculated summary scores for each ability and assessed their reliability and relationships with health status and use of health services. Results. 22% of the subjects reported difficulty walking 100 m, 15% were unable to run 10 m, and 50% had difficulty lifting 10 kg. Men reported higher abilities than women but differences according to age were small. Test-retest reliability ranged from 0.89 for walking to 0.88 for running and 0.81 for lifting. Scores for the three measures correlated with other measures of health status as expected. Conclusions. The study provided new data on self-reported walking, running, and lifting abilities among older Canadians. The new measures are valid, reliable, and easy to interpret. We expect these measures to be useful in clinical and research settings.


Essential oils from Piper aduncum inflorescences and leaves: chemical composition and antifungal activity against Sclerotinia sclerotiorum.
Even though essential oils from Piper aduncum (Piperaceae) have different biological activities, little is known about their application to agricultural areas. White mold is a plant disease caused by the phytopathogen Sclerotinia sclerotiorum, which needs to be controlled by alternative measures. This study aimed at evaluating the effect of essential oils from P. aduncum leaves (PL-EO) and inflorescences (PI-EO) on the mycelial growth of S. sclerotiorum. Essential oils from P. aduncum were obtained by hydrodistillation by a Clevenger-type apparatus while their chemical composition was analyzed by GC-MS and GC-FID. Piperitone (23.4 %), myristicin (12.4 %), terpinen-4-ol (12.3 %), β-caryophyllene (7.2 %), α-humulene (6.9 %), germacrene-D (6.9 %) and dillapiol (6.3 %) were the main constituents found in oils from P. aduncum. The in vitro antifungal activity showed that PI-EO dose above 30 µL inhibited mycelial growth in 100 %, whereas PL-EO at 50 µL inhibited it in 98.74 %. This is the first report of the chemical composition of PI-EO and results suggest that the essential oils under evaluation have high potential to control the phytopathogenic fungus S. sclerotiorum.


Examining the relationship between the reconstructed scales and the fake bad scale of the MMPI-2.
This study explores the relationship between the Reconstructed (RC) scales and the Fake Bad Scale (FBS) of the MMPI-2 in the context of a personal injury population to demonstrate which RC scales are susceptible to symptom exaggeration. The sample consisted of 76 compensation-seeking participants who were assessed for neurocognitive dysfunction. A multiple regression analysis was performed to determine the association between the Reconstructed Scale T-scores with the FBS T-scores. Three of the nine RC scales (RC1, RC2, RC3) were significantly (p <. 05) associated with FBS, with RC7 demonstrating a strong trend (p =. 0526). These scale scores accounted for approximately 66% of the variation in the FBS score. The RC1 scale accounted for the most variation (R(2) =. 53). Results suggest that the RC scales are susceptible to exaggeration of somatic concerns and non-psychotic emotional distress.